Biologically compatible materials capable of being formed into implants are increasing in use in surgery and medicine. Examples include vascular grafts, ligament prostheses and reconstructive patches.
Utilization of surgical implants presents several problems to the practitioner. For example, the potential of infections exists with surgically placed implants, including grafts, prostheses, etc. See e.g., E. J. Young and B. Sugarman, Infections in Prosthetic Devices, 68 Surg. Clin. N. Am., 167 (1988); The International Journal of Periodontics and Restorative Dentistry, April (1988); B. Van der Lei, et al., Expanded Polytetrafluoroethylene Patch for the Repair of Large Abdominal Wall Defects, 76 Br. J. Surg., 803 (1989); N. S. Horbach, et al., A Suburethral Sling Procedure with Polytetrafluoroethylene for the Treatment of Genuine Stress Incontinence in Patients with low Urethral Closure Pressure, 71 Obstete. Gynecol., 648 (1988).
Adverse clotting problems can also occur with vascular grafts. N. A. Schoenfeld, et al., A New Primate Model for the Study of Intravenous Thrombotic Potential and its Modification, 8 J. Vasc. Surg., 49 (1988); L. J. Dacey, et al., Intraarterial 9-beta-methyl carbacyclin Improves Canine Polytetrafluoroethylene Graft Patency, 8 J. Vasc. Surg., 21 (1988).
Potential infection and excessive inflammation can create problems with orthopedic prostheses. See e.g., E. J. Young and B. Sugarman, supra; S. P. F. Hughes, Treatment of Infected Implants, Antibiotic Acrylic Composites, 16 Orthopaedic Review, 233 (1987); J. H. Roth, et al., Synovial Reaction Associated with Disruption of Polypropylene Braid-augmented Intraarticular Anterior Cruciate Ligament Reconstruction, 16 Am.J. Sports Med., 301 (1988); S. K. Ahlfeld, et al., Anterior Cruciate Reconstruction in the Chronically Unstable Knee using an Expanded Polytetrafluoroethylene (PTFE) Prosthetic Ligament, 15 Am.J. Sports Med., 326 (1987).
Accordingly, the "take" of these implants, such as a cruciate ligament prosthesis, is variable.
Chemotherapeutic agents have been previously incorporated into vascular grafts. For example, U.S. Pat. No. 4,321,711 discloses a vascular prosthesis comprising porous tubing of polytetrafluoroethylene containing an anti-coagulant substance with a porous elastomer coating, containing a substance which counteracts the anti-coagulant, bonded to its outside surface. Typically, the anti-coagulant substance is heparin. Any heparin antagonist such as protamine may be used in the elastomer coating to counteract the heparin. U.S. Pat. No. 4,816,339 also refers to the use of therapeutically active substances, such as heparin or antibiotics, placed into an elastomer solution which surrounds a luminal polytetrafluoroethylene layer. However, the incorporated chemotherapeutic agents are soon exhausted from these implants, resulting in renewed potential for clotting. Thus, neither of these inventions provide for the sustained, controlled release of chemotherapeutic agents, nor the enhanced cellular uptake of these agents, that the present invention would provide.
The present invention solves these and many other problems associated with surgical implantation, successful grafting and tissue regeneration.